Dynamic bioactive bone graft material and methods for handling

ABSTRACT

The present disclosure relates to a dynamic bioactive bone graft material and a method of handling the material to prepare an implant. In one embodiment, a method of preparing a dynamic bioactive bone graft implant is provided. The method includes the step of providing a porous, fibrous composition of bioactive glass fibers, wherein the fibers are characterized by fiber diameters ranging from about 5 nanometers to about 100 micrometers, and wherein the porosity of the matrix ranges from about 100 nanometers to about 1 millimeter. The porous, fibrous composition is introduced into a mold tray, and a shaped implant is created using the mold tray. The composition may be wetted with a fluid such as saline or a naturally occurring body fluid like blood prior to creating the shaped implant. In another embodiment, the porous, fibrous composition is provided with the mold tray as a kit.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims priority to U.S. Provisional Patent ApplicationNo. 61/389,983, filed Oct. 5, 2010, and entitled “DYNAMIC BIOACTIVE BONEGRAFT MATERIAL AND METHODS FOR HANDLING,” and to U.S. Provisional PatentApplication No. 61/256,287, filed Oct. 29, 2009, and entitled “BONEGRAFT MATERIAL,” both of which are herein incorporated by reference intheir entirety. This application is also related to co-pending U.S.patent application Ser. No. 12/437,531, filed May 7, 2009, and entitled“DYNAMIC BIOACTIVE NANOFIBER SCAFFOLDING,” which claims priority to U.S.Provisional Application No. 61/127,172, filed on May 12, 2008 of thesame title.

FIELD

The present disclosure relates generally to bone graft materials andmethods of handling such materials. More particularly, the presentdisclosure relates to a dynamic bioactive synthetic bone graft material,and associated methods of handling the material for preparing an implantfor repairing or restoring bone tissue.

BACKGROUND

There has been a continuing need for improved bone graft materials.Known autograft materials have acceptable physical and biologicalproperties and exhibit the appropriate structure for bone growth.However, the use of autogenous bone requires the patient to undergomultiple or extended surgeries, consequently increasing the time thepatient is under anesthesia, and leading to considerable pain, increasedrisk of infection and other complications, and morbidity at the donorsite.

Alternatively, allograft devices may be used for bone grafts. Allograftdevices are processed from donor bone. Allograft devices may haveappropriate structure with the added benefit of decreased risk and painto the patient, but likewise incur the increased risk arising from thepotential for disease transmission and rejection. Autograft andallograft devices are further restricted in terms of variations on shapeand size.

Unfortunately, the quality of autograft and allograft devices isinherently variable, because such devices are made from harvestednatural materials. Likewise, autograft supplies are also limited by howmuch bone may be safely extracted from the patient, and this amount maybe severely limited in the case of the seriously ill or weak.

A large variety of synthetic bone graft materials are currentlyavailable for use. Recently, new materials, such as bioactive glass(“BAG”) particulate based materials, have become an increasingly viablealternative or supplement to natural bone- derived graft materials.These new (non-bone derived) materials have the advantage of avoidingpainful and inherently risky harvesting procedures on patients. Also,the use of non-bone derived materials can reduce the risk of diseasetransmission. Like autograft and allograft materials, these newartificial materials can serve as osteoconductive scaffolds that promotebone regrowth. Preferably, the graft material is resorbable and iseventually replaced with new bone tissue.

Many artificial bone grafts available today comprise materials that haveproperties similar to natural bone, such as compositions containingcalcium phosphates. Exemplary calcium phosphate compositions containtype-B carbonated hydroxyapatite [Ca₅(PO₄)_(3x)(CO₃)_(x)(OH)]. Calciumphosphate ceramics have been fabricated and implanted in mammals invarious forms including, but not limited to, shaped bodies and cements.Different stoichiometric compositions, such as hydroxyapatite (HA),tricalcium phosphate (TCP), tetracalcium phosphate (TTCP), and othercalcium phosphate (CaP) salts and minerals have all been employed inattempts to match the adaptability, biocompatibility, structure, andstrength of natural bone. Although calcium phosphate based materials arewidely accepted, they lack the ease of handling, flexibility andcapacity to serve as a liquid carrier/storage media necessary to be usedin a wide array of clinical applications. Calcium phosphate materialsare inherently rigid, and to facilitate handling are generally providedas part of an admixture with a carrier material; such admixturestypically have an active calcium phosphate ingredient to carrier ratioof about 50:50, and may have as low as 10:90.

The roles of porosity, pore size and pore size distribution in promotingrevascularization, healing, and remodeling of bone have been recognizedas important contributing factors for successful bone graftingmaterials. However, currently available bone graft materials still lackthe requisite chemical and physical properties necessary for an idealgraft material. For instance, currently available graft materials tendto resorb too quickly, while some take too long to resorb due to thematerial's chemical composition and structure. For example, certainmaterials made from hydroxyapatite tend to take too long to resorb,while materials made from calcium sulphate or B-TCP tend to resorb tooquickly. Further, if the porosity of the material is too high (e.g.,around 90%), there may not be enough base material left after resorptionhas taken place to support osteoconduction. Conversely, if the porosityof the material is too low (e.g., 30%,) then too much material must beresorbed, leading to longer resorption rates. In addition, the excessmaterial means there may not be enough room left in the residual graftmaterial for cell infiltration. Other times, the graft materials may betoo soft, such that any kind of physical pressure exerted on them duringclinical usage causes them to lose the fluids retained by them.

Thus, there remains a need for improved bone graft materials thatprovide the necessary biomaterial, structure and clinical handlingnecessary for optimal bone grafting. What is also needed are dynamicbone graft materials that provide an improved mechanism of action forbone grafting, by allowing the new tissue formation to be achievedthrough a physiologic process rather than merely from templating. Therelikewise remains a need for an artificial bone graft material that canbe manufactured as required to possess varying levels of porosity, suchas nano, micro, meso, and macro porosity. Further, a need remains for abone graft material that can be selectively composed and structured tohave differential or staged resorption capacity, while providingmaterial than can be easily molded or shaped into clinically relevantshapes as needed for different surgical and anatomical applications. Inparticular, it would be highly desirable to provide a bone graftmaterial that includes the characteristics of variable degrees ofporosity, differential bioresorbability, compression resistance andradiopacity, and also maximizes the content of active ingredientrelative to carrier materials such as collagen. Even more desirablewould be a bone graft material that possesses all of the advantagesmentioned above, and includes antimicrobial properties as well asallowing for drug delivery that can be easily handled in clinicalsettings. Embodiments of the present disclosure address these and otherneeds.

SUMMARY

The present disclosure provides bioactive bone graft materials andmethods for handling the bone graft materials. These graft materials aredynamic and accordingly can be molded and shaped as desired. These bonegraft materials address the unmet needs aforementioned by providing thenecessary biomaterial, structure and clinical handling for optimal bonegrafting. In addition, these bone graft materials provide an improvedmechanism of action for bone grafting, by allowing the new tissueformation to be achieved through a physiologic process of induction andformation rather than merely from templating and replacement. Further,these artificial bone graft materials can be manufactured as required topossess varying levels of porosity, such as nano, micro, meso, and macroporosity. The bone graft materials can be selectively composed andstructured to have differential or staged resorption capacity, whilebeing easily molded or shaped into clinically relevant shapes as neededfor different surgical and anatomical applications. Additionally, thesebone graft materials may have variable degrees of porosity, differentialbioresorbability, compression resistance and radiopacity, and can alsomaximize the content of active ingredient relative to carrier materialssuch as collagen. These bone graft materials also possess antimicrobialproperties as well as allows for drug delivery. The materials can alsobe easily handled in clinical settings.

In one embodiment, a method of preparing a dynamic bioactive bone graftimplant is provided. The method includes the step of providing a porous,fibrous composition of bioactive glass fibers, wherein the fibers arecharacterized by fiber diameters ranging from about 5 nanometers toabout 100 micrometers, and wherein the porosity of the matrix rangesfrom about 100 nanometers to about 1 millimeter. The porous, fibrouscomposition is introduced into a mold tray, and a shaped implant iscreated with the mold tray. The composition may be wetted with a fluidsuch as saline or a naturally occurring body fluid like blood prior tocreating the shaped implant.

The mold tray may comprise a base component and a lid componentconfigured to fit onto the base component to form an enclosed container.The implant may be created using applied force such as manual pressure,or vacuum pressure. For example, the force may be from simply fillingthe mold tray with the material. In one embodiment, the applied forcecompresses the porous, fibrous composition. The composition may remaincompressed after the force has been removed.

In another embodiment, a kit for preparing a dynamic bioactive bonegraft implant is provided. The kit includes a porous, fibrouscomposition of bioactive glass fibers, wherein the fibers arecharacterized by fiber diameters ranging from about 5 nanometers toabout 100 micrometers, and wherein the porosity of the matrix rangesfrom about 100 nanometers to about 1 millimeter. The kit also includes amold tray having a base component and a lid component configured to nestwithin the base component. Each of the base and lid components may havecorresponding depressed or raised portions to form a predefined moldedshape.

The mold tray may be sterile. In addition, the base component and lidcomponent form an enclosed container when attached together. The lidcomponent may further include tabs for ease of handling. The basecomponent may have more than one preformed well for creating a shapedmold. Accordingly, more than one shape may be created with the same moldtray. That shape may be, for example, a rectangle, square, disc,crescent, star, wave, diamond, C-shape, W-shape, S-shape, or T-shape.Further, the predefined molded shape may have rounded edges to create asmooth implant. Alternatively, the predefined molded shape may have atapered leading edge for ease of implantation. The molded tray may bedisposable.

BRIEF DESCRIPTION OF THE DRAWINGS

The foregoing and other features of the present disclosure will becomeapparent to one skilled in the art to which the present disclosurerelates upon consideration of the following description of exemplaryembodiments with reference to the accompanying drawings. In the Figures:

FIG. 1A is an illustration of a dynamic fibrous bioactive glass matrixaccording to a first embodiment of the present disclosure.

FIG. 1B is an enlarged view of the matrix of FIG. 1A.

FIG. 2A is a perspective view of a first interlocking, entangled porousconstruct formed of the fibrous bioactive glass matrix of FIG. 1.

FIG. 2B is a perspective view of a second interlocking, entangled porousconstruct formed of the fibrous bioactive glass matrix of FIG. 1.

FIG. 2C is a perspective view of a third interlocking, entangled porousconstruct formed of the fibrous bioactive glass matrix of FIG. 1.

FIG. 3A is an illustration of a dynamic bioactive glass matrix havingboth fibers and particulate according to another embodiment of thepresent disclosure.

FIG. 3B is an enlarged view of the matrix of FIG. 3A.

FIG. 4A is an illustration of an exemplary bioactive glass fiber bonegraft material according to the present disclosure having an organizedparallel fiber arrangement with descending layers of fibers incross-directional relationship to alternating layers of fibers.

FIG. 4B is an illustration of an exemplary bioactive glass fiber bonegraft material in a randomly arranged spun-glass structure withbioactive glass particulate.

FIG. 4C is an illustration of an exemplary bioactive glass fiber bonegraft material constructed as a mesh with descending layers of fibersbeing arranged so as to have a different degree of porosity relative tothe previous layer of fibers, thus providing a cell filterfunctionality.

FIG. 5A is a perspective view of a packaging container according to amedical kit embodiment of the present disclosure.

FIG. 5B is a perspective view of the embodiment of FIG. 5A includingfibrous bioactive bone graft material positioned in the kit.

FIG. 5C is a perspective view of the bone graft material of FIG. 5Bremoved from the kit.

FIGS. 6A-6D show different embodiments of a packaging container and moldtray according to the present disclosure.

FIGS. 7A-7L illustrate various methods for creating a shaped or moldedbone graft material in accordance with the present disclosure.

DETAILED DESCRIPTION OF THE EMBODIMENTS

The standard method for healing natural tissue with synthetic materialshas been to provide a device having the microstructure andmacrostructure of the desired end product. Where the desired end productis cancellous bone, traditional bone grafts have been engineered tomimic the architecture of cancellous bone. Although this has been thecurrent standard for bone grafts, it does not take into account the factthat bone is a living tissue. Each bony trabeculae is constantlyundergoing active biologic remodeling in response to load, stress and/ordamage. In addition, cancellous and cortical bone also support a vastnetwork of vasculature. This network not only delivers nutrients tosustain the living environment surrounding bone, but also supports redblood cells and marrow required for basic biologic function. Therefore,merely providing a synthetic material with the same architecture that isnon-biologic is insufficient for optimal bone healing and bone health.Instead, what is required is a mechanism that can recreate the livingstructure of bone.

Traditional synthetics act as a cast, or template, for normal bonetissue to organize and form. Since these synthetics are not naturallyoccurring, eventually the casts or templates have to be resorbed toallow for normal bone to be developed. If these architectured syntheticsdo not resorb and do not allow proper bone healing, they simply becomeforeign bodies that are not only obstacles, but potentially detrimental,to bone healing. This phenomenon has been observed in many studies withslow resorbing or non-resorbing synthetics. Since these synthetics arejust inert, non-biologic structures that only resemble bone, they behaveas a mechanical block to normal bone healing and development.

With the understanding that bone is a living biologic tissue and thatinert structures will only impede bone healing, a different physiologicapproach is presented with the present invention. Healing is a phasicprocess starting with some initial reaction. Each phase builds on thereaction that occurred in the prior phase. Only after a cascade ofphases does the final development of the end product occur—bone. Thetraditional method has been to replace or somehow stimulate healing byplacing an inert final product as a catalyst to the healing process.This premature act certainly does not account for the physiologicprocess of bone development and healing.

The physiologic process of bone healing can be broken down to threephases: (a) inflammation; (b) osteogenesis; and (c) remodeling.Inflammation is the first reaction to injury and a natural catalyst byproviding the chemotactic factors that will initiate the healingprocess. Osteogenesis is the next phase where osteoblasts respond andstart creating osteoid, the basic material of bone. Remodeling is thefinal phase in which osteoclasts and osteocytes then recreate thethree-dimensional architecture of bone.

In a normal tissue repair process, at the initial phase a fibrin clot ismade that provides a fibrous architecture for cells to adhere. This isthe cornerstone of all connective tissue healing. It is this fibrousarchitecture that allows for direct cell attachment and connectivitybetween cells. Ultimately, the goal is to stimulate cell proliferationand osteogenesis in the early healing phase and then allow forphysiologic remodeling to take place. Since the desired end product is aliving tissue and not an inert scaffold, the primary objective is tostimulate as much living bone as possible by enhancing the natural fibernetwork involved in initiation and osteogenesis.

The bone graft material of the present disclosure attempts torecapitulate the normal physiologic healing process by presenting thefibrous structure of the fibrin clot. Since this bioactive material madeof fibers is both osteoconductive as well as osteostimulative, thisfibrous network will further enhance and accelerate bone induction.Further, the dynamic nature of the bioactive fibrous matrix or scaffoldallows for natural initiation and stimulation of bone formation ratherthan placing a non-biologic template that may impede final formation aswith current graft materials. The fibers of the present material canalso be engineered to provide a chemical reaction known to selectivelystimulate osteoblast proliferation or other cellular phenotypes.

The present disclosure provides bone graft materials and bone graftimplants formed from these materials. These bone graft materials providethe necessary biomaterial, structure and clinical handling for optimalbone grafting. In addition, these bone graft materials provide animproved mechanism of action for bone grafting, by allowing the newtissue formation to be achieved through a physiologic process ratherthan merely from templating. Further, these artificial bone graftmaterials can be manufactured as required to possess varying levels ofporosity, such as nano, micro, meso, and macro porosity. The bone graftmaterials can be selectively composed and structured to havedifferential or staged resorption capacity, while being easily molded orshaped into clinically relevant shapes as needed for different surgicaland anatomical applications. Additionally, these bone graft materialsmay have variable degrees of porosity, differential bioresorbability,compression resistance and radiopacity, and can also maximize thecontent of active ingredient relative to carrier materials such ascollagen. These bone graft materials also possess antimicrobialproperties as well as allows for drug delivery. The materials can alsobe easily handled in clinical settings, and can be provided in kits thatallow for a hands-free, controlled environment for manipulating thematerial.

Embodiments of the present disclosure may employ a dynamic, ultraporousbone graft material, for example, having nano, micro, meso and macroporosities. The bone graft material can comprise bioactive (“BAG”)fibers or a combination of BAG fibers and particulates of materials. Thebone graft material is a dynamic structure that can be molded or packedinto a desired shape. The bone graft material may be osteoconductiveand/or osteostimulatory. By varying the diameter and chemicalcomposition of the components used in the embodiments, the bone graftmaterial may have differential activation (i.e., resorbability), whichmay facilitate advanced functions like drug delivery includingantibiotics. Furthermore, the fibrous nature of the bone graft materialhelps facilitate in situ catalytic conversion of fibrinogen to fibrin bythrombin to form cross-linked fibrin clots or matrix, thereby providingfiber mediated healing which is essential for any kind of connectivetissue healing.

The embodiments of the bone graft material can include BAG fibers havinga relatively small diameter, and in particular, a diameter less than 100nanometers. In one embodiment, the fiber diameter can be less than 10nanometers, and in another embodiment, the fiber diameter can be in therange of about 5 nanometers. Since the materials used in the embodimentsare bioactive materials, the bone graft material may form a CaP layer onits surface when it interacts with body fluids.

In other embodiments, the bone graft material may comprise particulatesin combination with fibers. The presence of particulate matter may beemployed to modify or control the resorption rate and resorption profileof the bone graft material as well as provide mechanical strength andcompression resistance. The particulate may be bioactive glass, calciumsulfate, calcium phosphate or hydroxyapatite. The particulate may besolid, or it may be porous.

The bone graft material may be moldable and can be packaged infunctional molds for convenient clinical handling. In addition, the bonegraft material can be mixed with other additives like collagen, etc.,for example, to further facilitate handling. The bone graft material andcollagen composite may be in the form of a foam, and the foam mayadditionally be shaped into a strip, a continuous rolled sheet, a spongeor a plug. However, it is understood that the foam may take anyconfiguration with any variety of shapes and sizes. In addition, thebone graft material and collagen composite may take the form of a puttyor other moldable material. For example, in one embodiment, the BAGfibers and particulates may be mixed with a slurry of collagen, pouredinto a mold of a desired shape, and frozen to yield a desire foam shape.In another example depending upon the type of collaged used, the foamcan have a fixed shape or the foam may be turned into a putty with theaddition of fluids such as saline, blood or bone marrow aspirate.Alternatively, the bone graft material may be in the form of aninjectable material.

Putties can be made by combining the bone graft material with otheradditives such as CMC, hyaluronic acid, or sodium alginate, forinstance. The ability to provide a bone graft material in the form of aputty renders the material easily usable, since the putty may be applieddirectly to the injury site by either injection or by plastering. Also,the ease of handling and moldability of the putty composition allows theclinician to form the material easily and quickly into any desiredshape.

Reference will now be made to the embodiments illustrated in thedrawings. It will nevertheless be understood that no limitation of thescope of the present disclosure is thereby intended, with suchalterations and further modifications in the illustrated device and suchfurther applications of the principles of the present disclosure asillustrated therein being contemplated as would normally occur to oneskilled in the art to which the present disclosure relates.

The present disclosure relates to a synthetic bone graft material thatcan be manufactured in a wide variety of compositional and structuralforms for the purpose of introducing a biocompatible, bioabsorbablestructural matrix in the form of an implant for the repair or treatmentof bone. The bone graft material can be an osteostimulative and/orosteoconductive implant having differential bioabsorbability. In someembodiments, the bone graft material may be substantially comprised ofBAG fibers.

In one embodiment, the bone graft material can be selectively determinedby controlling compositional and manufacturing variables, such asbioactive glass fiber diameter, size, shape, and surface characteristicsas well as the amount of bioactive glass particulate content andstructural characteristics, and the inclusion of additional additives,such as, for example tricalcium phosphate, hydroxyapatite, and the like.By selectively controlling such manufacturing variables, it is possibleto provide an artificial bone graft material having selectable degreesof characteristics such as porosity, bioabsorbability, tissue and/orcell penetration, calcium bioavailability, flexibility, strength,compressibility and the like. These and other characteristics of thedisclosed bone graft material are discussed in greater detail below.

The bioactive glass used in the bone graft material may have acomposition similar to 45S5 (46.1 mol % SiO₂, 26.9 mol % CaO, 24.4 mol %Na₂O and 2.5 mol % P₂O₅, 58S (60 mol % SiO₂, 36 mol % CaO and 4 mol %P₂O₅), S70C30 (70 mol % SiO₂, 30 mol % CaO), and the like. Of course,bioactive glasses that are silicon free may also be employed. Forexample, bioactive glass compositions that are SiO₂ free, and havingboron instead of silicon, may also be used. The bone graft material maybe tailored to have specific desired characteristics, such as increasedX-ray opacity (for example, by incorporating strontium), slower orfaster dissolution rate in vivo, surface texturing, or the like.

The bone graft material may serve as a scaffold for bone activity in thebone defect. The scaffolding materials used in the bone graft may bebioactive glasses, such as 45S5 glass, which can be both osteoconductiveand osteostimulatory. As determined by applicants, the bioactive glassmay have naturally inherent antimicrobial properties due to the presenceof sodium in the material's composition. The extensive surface areaprovided by the present fibrous bone graft material allows forantimicrobial benefits with the use of this material.

Bone graft materials of the present disclosure can be flexible,moldable, or can be preformed to mimic, augment or replace specificshaped structures. For example, the bone graft materials can be formedinto acetabulum cups and other skeletal modeled components employed insurgical procedures. The bone graft materials can be formed into anyclinically useful shape, such as strips, blocks, wedges, and the like.The shapes may be formed by molding, as will be described in greaterdetail below, or simply by cutting, tearing, folding, or separating thefibrous material into the desired configuration for its clinicalapplication

In the embodiments, the bone graft material is formed from bioactiveglass fibers, which may be manufactured having predeterminedcross-sectional diameters sized as desired. The fibers may be formed byelectro spinning or laser spinning, for instance, to create consistentlyuniform fibers. In one embodiment, the bone graft material may be formedfrom a scaffold of fibers of uniform diameters. Further, the bioactiveglass fibers may be formed having varying diameters and/orcross-sectional shapes, and may even be drawn as hollow tubes.Additionally, the fibers may be meshed, woven, intertangled and the likefor provision into a wide variety of shapes.

For example, a bioactive glass fiber bone graft material manufacturedsuch that each fiber is juxtaposed or out of alignment with the otherfibers could result in a bone graft material having a glass-wool or“cotton-ball” appearance due to the large amount of empty space createdby the random relationship of the individual glass fibers within thematerial. Such a manufacture enables a bone graft material with anoverall soft or pliable texture so as to permit the surgeon to manuallyform the material into any desired overall shape to meet the surgical oranatomical requirements of a specific patient's surgical procedure. Suchmaterial also easily lends itself to incorporating additives randomlydispersed throughout the overall bone graft material, such as includedbioactive glass particles, antimicrobial fibers, particulate medicines,trace elements or metals such as copper, which is a highly angiogenicmetal, strontium, magnesium, zinc, etc. mineralogical calcium sources,and the like. Further, the bioactive glass fibers may also be coatedwith organic acids (such as formic acid, hyaluronic acid, or the like),mineralogical calcium sources (such as tricalcium phosphate,hydroxyapatite, calcium sulfate, or the like), antimicrobials,antivirals, vitamins, x-ray opacifiers, or other such materials.

The bone graft material may be engineered with fibers having varyingresorption rates. The resorption rate of a fiber is determined orcontrolled by its material composition and by its diameter. The materialcomposition may result in a slow reacting vs. faster reacting product.Similarly, smaller diameter fibers can resorb faster than largerdiameter fibers. Also, the overall porosity of the material can affectresorption rate. Materials possessing a higher porosity mean there isless material for cells to remove. Conversely, materials possessing alower porosity mean cells have to do more work, and resorption isslower. Accordingly, the bone graft material may contain fibers thathave the appropriate material composition as well as diameter foroptimal performance. A combination of different fibers may be includedin the material in order to achieve the desired result.

As with the bioactive glass fibers, the inclusion of bioactive glassparticles can be accomplished using particles having a wide range ofsizes or configurations to include roughened surfaces, very largesurface areas, and the like. For example, particles may be tailored toinclude interior lumens with perforations to permit exposure of thesurface of the particles interior. Such particles would be more quicklyabsorbed, allowing a tailored material characterized by differentialresorbability. The perforated or porous particles could be characterizedby uniform diameters or uniform perforation sizes, for example. Theporosity provided by the particles may be viewed as a secondary range ofporosity accorded the bone graft material or the implant formed from thebone graft material. By varying the size, transverse diameter, surfacetexture, and configurations of the bioactive glass fibers and particles,if included, the manufacturer has the ability to provide a bioactiveglass bone graft material with selectively variable characteristics thatcan greatly affect the function of the material before and after it isimplanted in a patient. The nano and macro sized pores provide superbfluid soak and hold capacity, which enhances the bioactivity andaccordingly the repair process.

FIGS. 1A and 1B illustrate a first embodiment bioactive fibrous scaffold10 according to the present disclosure. The scaffold 10 is made up of aplurality of interlocking fibers 15 defining a three-dimensional poroussupport scaffold or matrix 10. The support matrix 10 is made up ofbioactive glass fibers 10 that are interlocked or interwoven, notnecessarily fused at their intersections 17. At least some of the fibers15 may thus move over one another with some degree of freedom, yieldinga support web 10 that is dynamic in nature. The composition of thefibers 15 used as the struts 19 of the resulting dynamic fibrousscaffold 10 are typically bioactive glass, ceramic or glass-ceramicformulations, such that within the range of fiber diameter and constructsize, that the scaffolding fibers 15 are generally characterized ashaving the attributes of bioactivity.

The diameters of the fibers 15 defining the dynamic scaffold 10 aretypically sufficiently small to allow for inherent interlocking of theresulting three-dimensional scaffold 10 upon itself, without the needfor sintering, fusing or otherwise attaching the fibers 15 at theirintersections 17, although some such fusing or attachment may beemployed to further stiffen the scaffold 10 if desired. Hence thescaffold 10 is self constrained to not completely fall apart, yet theindividual fibers 15 defining the support struts 19 are free to movesmall distances over each other to grant the scaffold 10 its dynamicqualities such that it remains flexible while offering sufficientsupport for tissue formation and growth thereupon. In addition, theavailability of nano sized fibers can significantly enhance the surfacearea available for cell attachment and reactivity.

As will be described in detail below, pluralities of fibers 15characterized as substantially having diameters below 1 micrometer (1000nanometers) are sufficient to form dynamic scaffolding 10, as arepluralities of fibers 15 characterized as substantially having diametersbelow 100 nanometers. The scaffolding 10 may also be constructed from aplurality of fibers 15 having multi-modal diameter distributions,wherein combinations of diameters may be employed to yield specificcombinations of dynamic flexibility, structural support, internal voidsize, void distribution, compressibility, dissolution and resorptionrates, and the like. For example, some of the fibers 15 may be fastreacting and resorb quickly into bone to induce initial bone growth. Inaddition, some remnant materials of the bone graft material, such asother fibers 15 or particulates, may be designed to resorb over a moreextended time and continue to support bone growth after the previouslyresorbed material has gone. This type of layered or staged resorptioncan be critically important in cases where the surgical site has notsufficiently healed after the first burst of bone growth activity. Byproviding varying levels of resorption to occur, the material allowsgreater control over the healing process and avoids the “all or none”situation.

Typically, the ranges of fiber diameters within a construct rangestarting from the nano level, where a nano fiber is defined as a fiberwith a diameter less than 1 micron (submicron), up to about 100 microns;more typically, fiber diameters range from about 0.005 microns to about10 microns; still more typically, fiber diameters range from about 0.05to about 6 microns; yet more typically, fiber diameters range from 0.5to about 20 microns; still more typically, fiber diameters range fromabout 1 micron to about 6 microns. In all cases, predetermined amountsof larger fibers may be added to vary one or more of the properties ofthe resultant scaffolding 10 as desired. It should be noted that as theamount of smaller (typically less than 10 micrometer) diameter fibers 15decreases and more of the scaffolding construct 10 contains fibers 15 ofrelatively greater diameters, the entire construct 10 typically tends tobecome less self constrained. Thus, by varying the relative diametersand aspect ratios of constituent fibers 15 the resulting scaffoldstructure 10 may be tailored to have more or less flexibility and lessor more load-bearing rigidity. Furthermore, fibers 15 may be constructedat a particular size, such as at a nano scale of magnitude, to enhancethe surface area available for cell attachment and reactivity. In oneembodiment, the bone graft material includes at least one nanofiber. Inone embodiment, the bone graft material includes at least one nanofiber.

One factor influencing the mechanism of a dynamic scaffold 10 is theincorporation of relatively small diameter fibers 15 and the resultingimplant 20. Porous, fibrous scaffolds 10 may be made by a variety ofmethods resulting in an interlocking, entangled, orientatedthree-dimensional fiber implant 20.

As illustrated in FIGS. 1A and 1B, these fibers 15 are not necessarilycontinuous, but may be short and discrete, or some combination of long,continuous fibers 15 and short, discrete fibers 15. The fibers 15 touchto define intersections 17 and also define pores or voids 37. By varyingthe fiber dimensions and interaction modes, the porosity of theresulting implant, as well as its pore size distribution, may becontrolled. This enables control of total porosity of the implant (up toabout 95% or even higher) as well as control of pore size anddistribution, allowing for materials made with predetermined nano-(porediameters less than about 1 micron and as small as 100 nanometers oreven smaller), micro-(pore diameters between about 1 and about 10microns), meso-(pore diameters between about 10 and about 100 microns),and macro-(pore diameters in excess of about 100 microns and as large as1 mm or even larger) porosity. The pores 37 typically range in size fromabout 100 nanometers to about 1 mm, with the pore size and sizedistribution a function of the selected fiber size range and sizedistribution, as well as of the selected forming technique. However, itis understood that the fiber and pore size is not limited to theseranges, and while the description focuses on the nanofibers andnanopores, it is well understood that the bone graft material of thepresent disclosure may equally include macro sized fibers and pores tocreate range of diameters of fibers and pores.

An example of the effect of one distribution of pore size within anexemplary implant 20 and its volumetric contribution and surface areacontribution is shown with reference to FIGS. 8A and 8B, which arefurther described below. The resulting implant or device 20 may thus bea nonwoven fabric made via a spunlaid or spun blown process, a meltblown process, a wet laid matt or ‘glass tissue’ process, or the likeand may be formed to have the characteristics of a felt, a gauze, acotton ball, cotton candy, or the like.

Typically, macro-, meso-, and microporosity occur simultaneously in thedevice 20 and, more typically, are interconnected. It is unnecessaryhere to excessively quantify each type of porosity, as those skilled inthe art can easily characterize porosity using various techniques, suchas mercury intrusion porosimetry, helium pycnometry, scanning electronmicroscopy and the like. While the presence of more than a handful ofpores within the requisite size range is needed in order to characterizea device 20 as having a substantial degree of that particular type ofporosity, no specific number or percentage is called for. Rather, aqualitative evaluation by one skilled in the art shall be used todetermine macro-, meso-, micro-, and/or nanoporosity. In someembodiments, the overall porosity of the porous, fibrous implants 20will be relatively high, as measured by pore volume and typicallyexpressed as a percentage. Zero percent pore volume refers to a fully ortheoretically dense material. In other words, a material with zeroporosity has no pores at all. Likewise, one hundred percent pore volumewould designate “all pores” or air. One skilled in the art will beversed in the concept of pore volume and will readily be able tocalculate and apply it.

Bone graft implants 20 typically have pore volumes in excess of about30%, and more typically may have pore volumes in excess of 50% or 60%may also be routinely attainable. In some embodiments, scaffoldingimplants 20 may have pore volumes of at least about 70%, while otherembodiments may typically have pore volumes in excess of about 75% oreven 80%. Bone graft implants may even be prepared having pore volumesgreater than about 90%-97%.

It is advantageous for some bone graft implants 20 to have a porositygradient that includes macro-, meso-, and microporosity, and in somecases nanoporosity. The combination of fibers and particulates to createthe appropriate compression resistance and flexibility is retained whenthe bone graft implant 20 is wetted. Bone graft implants 20 are alsotypically characterized by interconnected porosity, as such iscorrelated with increased capillary action and wicking capability. Suchbone graft implants 20 should be capable of rapidly wicking andretaining liquid materials for sustained release over time.

The fibers 15 typically have non-fused linkages 35 that provide subtleflexibility and movement of the scaffolding 10 in response to changes inits environment, such as physiological fluctuations, cellular pressuredifferences, hydrodynamics in a pulsatile healing environment, and thelike. This in vivo environment can and will change over the course ofthe healing process, which may last as long as several months or evenlonger. The scaffold 10 typically retains its appropriate supportivecharacteristics and distribution of pores 37 throughout the healingprocess such that the healing mechanisms are not inhibited. During thehealing process, the pores 37 defined by the matrix of interlocking andtangled fibers 15 may serve to carry biological fluids and bone-buildingmaterials to the site of the new bone growth. The fluids likewise slowlydissolve fibers 15 made of bioactive glass and the like, such that thescaffolding 10, and particularly the pores 37, changes in size and shapein dynamic response to the healing process.

Scaffolds 10 are typically provided with a sufficiently permeablethree-dimensional microstructure for cells, small molecules, proteins,physiologic fluids, blood, bone marrow, oxygen and the like to flowthroughout the entire volume of the scaffold 10. Additionally, thedynamic nature of the scaffold 10 grants it the ability to detect orrespond to the microenvironment and adjust its structure 20 based onforces and pressure exerted elements within the microenvironment.

Additionally, scaffolds 10 typically have sufficient three-dimensionalgeometries for compliance of the bone graft implant or device 20 whenphysically placed into an irregular shaped defect, such as a void, hole,or tissue plane as are typically found in bone, tissue, or likephysiological site. The devices 20 typically experience some degree ofcompaction upon insertion into the defect, while the permeablecharacteristics of the scaffolds 10 are maintained. Typically, as withthe placement of any bone void filler, the device 20 remains within 2 mmof the native tissue in the defect wall.

Bone graft implants or devices 20 made from the scaffolding 10 canappear similar to felts, cotton balls, textile fabrics, gauze and thelike. These forms have the ability to wick, attach and contain fluids,proteins, bone marrow aspirate, cells, as well as to retain theseentities in a significant volume, though not necessarily all inentirety; for example, if compressed, some fluid may be expulsed fromthe structure.

Another advantage of the bone graft implants or devices 20 is theirability to modify or blend the dynamic fiber scaffolds 10 with a varietyof carriers or modifiers to improve handling, injectability, placement,minimally invasive injection, site conformity and retention, and thelike while retaining an equivalent of the ‘parent’ microstructure. Suchcarriers ideally modify the macro-scale handling characteristic of thedevice 20 while preserving the micro-scale (typically on the order ofless than 100 micrometers) structure of the scaffolding 10. Thesecarriers resorb rapidly (typically in less than about 2 weeks; moretypically in less than about 2 days) without substantially altering theform, microstructure, chemistry, and/or bioactivity properties of thescaffolding. These carriers include polaxamer, glycerol, alkaline oxidecopolymers, bone marrow aspirate, and the like.

FIG. 2A shows an embodiment of an implant 20 in the form of a strip orsheet, for example. FIG. 2B shows an embodiment of an implant 20 in theform of a three-dimensional structure similar to a cotton ball, forexample. In one example, a plurality of interlocking fibers 15 are spunor blown into a randomly-oriented assemblage 20 having the generalappearance of a cotton ball. The fibers 15 are typically characterizedas having diameters of from less than about 1000 nm (1 micrometer)ranging up to approximately 10, 000 nm (10 micrometers). The resultingcotton-ball device 20 may be formed with an uncompressed diameter oftypically from between about 1 and about 6 centimeters, although anyconvenient size may be formed, and may be compressible down to betweenabout ½ and ¼ of its initial size. In some cases, the device 20 cansubstantially return to its original size and shape once the compressiveforces are removed (unless it is wetted with fluids, which kind of locksthe device into desired shape and density, or is vacuum compressed).However, in many cases the device 20 may remain deformed. By varying therelative diameters of some of the fibers 15, structures ranging from‘cotton ball’ to ‘cotton candy’ may be produced, with varying ranges offiber diameters from less than about 10 nm to greater than about 10microns.

FIG. 2C shows an embodiment of the implant 20 in the form of a wovenmesh or fabric, for example. In one example, fibers 15 may be woven,knitted, or otherwise formed into a fabric device 20 having a gauze-likeconsistency. The fibers 15 are typically greater than 1 about micrometerin diameters and may be as large as about 100 micrometers in diameter.The micro-scale orientation of the fibers 15 is typically random,although the fibers may be somewhat or completely ordered. On amacro-scale, the fibers 15 are typically more ordered. The constituencyof these devices 20 may have varying amounts of smaller fibers 15incorporated therein to maintain the self constrained effect.

FIGS. 3A and 3B illustrate another embodiment of the present disclosure,a bioactive fibrous scaffold 110 as described above with respect toFIGS. 1A and 1B, but having glass microspheres or particulate 140distributed therethrough. The glass particulate 140 is typically made ofthe same general composition as the fibers 115, but may alternately bemade of other, different compositions. One advantage of the presence ofparticulate 140 in the implant 120 is its contribution to the implant's120 overall compression resistance. Since one function of the implant120 is typically to absorb and retain nutrient fluids that feed theregrowth of bone, it is advantageous for the implant to offer some levelof resistance to compressive forces, such that the liquids are notprematurely ‘squeezed out’. Particulate 140, whether spherical orparticulate, stiffens the implant, which is otherwise a porousscaffolding primarily composed of intertangled fibers 115. Theparticulate 140 can act as pillars, lending structural support to theoverall implant 120.

The glass particulate 140 is typically generally spherical, but may haveother regular or irregular shapes. The glass particulate 140 typicallyvaries in size, having diameters ranging from roughly the width of thefibers 115 (more typically, the struts 119) to diameters orders ofmagnitude greater than the typical fiber widths. Particulate 140 mayalso vary in shape, from generally spherical to spheroidal, orelliptical to irregular shapes, as desired. The particulate 140 may evenbe formed as generally flat platelets; further, the platelets (or othershapes) may be formed having perforations or internal voids, to increasethe effective surface area and dissolution rate. Likewise, the shape ofthe particulate 140 may be varied to influence such factors as bone cellattachment, particulate coatability, and the like.

In one embodiment, the glass particulates 140 may have an averagediameter of about 20 microns to about 1 millimeter. In anotherembodiment, the particulates 140 may have an average diameter of about300 to 500 microns. In still another embodiment, the glass particulates140 may have an average diameter of about 350 microns.

As with the fibers, bioactive glass particulate 140 may be coated withorganic acids (such as formic acid, hyaluronic acid, or the like),mineralogical calcium sources (such as tricalcium phosphate,hydroxyapatite, calcium sulfate, or the like), antimicrobials,antivirals, vitamins, x-ray opacifiers, or other such materials. Whilesmaller particulate may tend to lodge in or around fiber intersections117, larger particulate tend to become embedded in the scaffolding 120itself and held in place by webs of fibers 115. Pore-sized microspheresmay tend to lodge in pores 137.

The glass particulate 140 may be composed of a predetermined bioactivematerial and tailored to dissolve over a predetermined period of timewhen the scaffolding 110 is placed in vitro, so as to release apredetermined selection of minerals, bone growth media, and the like ata predetermined rate. The composition, size and shape of the glassparticulate 140 may be varied to tailor the resorption rate of thebioactive glass, and thus the rate at which minerals and the like areintroduced into the body (and, likewise, how long the particulate 140 isavailable to provide increased compression resistance to the scaffoldingimplant 20). For example, for a given bioactive glass composition andparticulate volume, irregularly shaped particulate 140 would have moresurface area than spherical particulate 140, and would thus dissolvemore rapidly.

Further, the glass particulate 140 may be hollow bioactive glass,polymer or the like microspheres filled with specific mixture ofmedicines, antibiotics, antivirals, vitamins or the like to be releasedat and around the bone regrowth site at a predetermined rate and for apredetermined length of time. The release rate and duration of releasemay be functions of particulate size, porosty and wall thickness as wellas the distribution function of the same.

As discussed above, the shape and texture of the bone graft material maybe randomly configured to maximize its overall volume, surface area, andpliability or, in stark contrast, can be manufactured with the bioactiveglass fibers in a more rigid and uniform arrangement, such as, forexample in a mesh or matrix type assembly. In a mesh or matrix assembly,as illustrated by the non-limiting examples shown in FIGS. 4A to 4C theglass fibers can be arranged in a stacked arrangement limiting theflexibility in a directional manner, or, the fibers can be layeredwherein alternating layers are in a crossed relationship one to theother. In FIG. 4A, the matrix assembly 110 is shown having an orderedconfiguration with discrete layers comprising fibers 115 and particulate140. In FIG. 4B, the matrix assembly is shown having a randomly arrangedconfiguration of fibers 115 and particulate 140 dispersed throughout. InFIG. 4C, the matrix assembly 110 is shown having a configuration inwhich the layers have different porosities due to differences in thespacing of the fibers 115 and particulate 140 throughout each layer.That is, the size of the pores 137 varies throughout the matrix assemblydue to the unevenly spaced fibers 115 and particulate 140. It should beunderstood that, while FIGS. 4A and 4C show discretely aligned fibers115 for the purposes of illustrating the concept herein, the individuallayers of material 110 may include fibers 115 and particulate 140 thatare unorganized and randomly aligned.

An advantage of the present disclosure is the wide variety ofalternative configurations and structural arrangements that result in anequally varied functionality of the material being used by a surgeon. Asillustrated in FIGS. 4A-C, the bone graft material of the presentdisclosure can include embedded bioactive glass particles within thebioactive glass fiber construct. The inclusion of such particles, asdetermined by the quantity, size, and characteristics of the particles,can affect the compressibility, bioabsorbability, and porosity of theresulting bone graft material. Additional additives, such as calciumphosphates (CaP), calcium sulfates (CaS), hydroxyapatite (HA),carboxymethycellulose (CMC), collagen, glycerol, gelatin, and the likecan also be included in any of the many varied constructions of thebioactive glass fiber bone graft material to assist in bone generationand patient recovery. Such additives may be in the range of 0 to 90percent porous. Another additive, collagen, may be included and may alsobe of the ultraporous kind having a porosity of up to 98 percent.

In one embodiment, the surface area of the bone graft material ismaximized to increase the bone ingrowth into the structural matrix ofthe material. Another useful variable is the capability of the bonegraft material to selectively be composed and configured to providelayers of varying porosity, such as nano-, micro-, meso-, andmicro-porosity, so as to act as a cell filter controlling the depth ofpenetration of selected cells into the material. Because the preparationof the bone graft material can be selectively varied to includebioactive glass fibers and/or particles having different cross-sectionaldiameters, shapes and/or compositions, the material properties may betailored to produce a bone graft material with differential absorptioncapabilities. This feature permits the surgeon to select a bone graftmaterial specifically for the needs of a specific situation or patient.Controlling the pace of bone ingrowth into the bioactive glass matrix ofthe material allows the surgeon to exercise almost unlimited flexibilityin selecting the appropriate bone graft material for an individualpatient's specific needs.

In another embodiment, the bioactive glass was formulated with strontiumpartially replacing calcium. The partial replacement of calcium withstrontium yields a bioactive glass with a reduced resorption/reactionrate and also with an increased radiodensity or radioopacity. Thus, thebioactive glass stays present in the body for a longer period of timeand also presents a more readily visible x-ray target.

In another embodiment, silver (or other antimicrobial materials) may beincorporated into the bioactive glass fiber scaffolding structuralmatrix. Silver is an antimicrobial material, and enhances the inherentantimicrobial properties of the bioactive glass material. Typically,silver is added as a dopant to very fine bioactive glass fibers, suchthat the silver is quickly released as the very fine fibers dissolve atthe implant site, allowing the silver to act as an anti-microbial agentto prevent infection immediately after surgery while the remainingscaffolding material does its work. Alternately, Ag may be introduced asfibers and interwoven with the bioactive glass fibers, as particlessimilar to the glass particulate discussed above, or the like. Ofcourse, varying the composition of the bioactive glass from which thefibers are formed to create an alkaline (high pH in the range of 8-10)glass may also provide the material with antimicrobial properties. Otherproperties and features of the material of the present disclosure aredescribed in a co-pending and commonly owned U.S. patent applicationSer. No. ______, entitled “DYNAMIC BIOACTIVE BONE GRAFT MATERIAL ANDMETHOD OF USE,” filed Oct. 28, 2010, the disclosure of which is herebyincorporated by reference.

One advantage of the graft material of the current disclosure is that itis dynamic, and can be easily molded into various shapes or form,without losing the essential structure and porosity. By packaging thematerial in a functional tray, where the tray acts as a mold, thematerial can be provided in various shapes in the operating room. Inparticular, the material becomes a cohesive mass when a fluid such asblood, saline, bone marrow, other natural body fluids, etc. is added.

In an embodiment, as shown in FIGS. 5A to 5C, the bone graft material isprovided as part of a surgical kit 200. The kit 200 includes a trayportion 210 having a recess or well 212, and more typically a set ofnested recesses, for storing, holding and manipulating the bone graftmaterial 10, 110, and a lid portion 220 for sealingly engaging the trayportion 210. The tray and lid portions 210, 220 are typically formedfrom thermoplastic materials, but may alternately be made of anyconvenient material. The deepest recess chamber 212 typically has asimple geometry, such as a rectangular block or wedge shape, such thatthe so-loaded bone graft material likewise has a simple geometry.

The bone graft material 10, 110 is typically provided as an intertangledor interwoven mass of bioactive glass fibers. The bioactive glass fibersmay be provided in format that is ready to be surgically emplaced in abony cavity (such as a woven or mesh format), or may be provided in aformat that requires additional preparation prior to emplacement (suchas a more loosely intertangled format) that requires the addition of aliquid, such as saline, glycerol, gelatin, plasma, or collagen gel orchips, to assist in rendering the mass of bioactive glass more pliableand structurally unitary. Such liquids may optionally be included in thekit packaging 200, or provided separately.

In one example, a kit 200 is provided, including a tray body 210 and alid 200 engagable with the tray body. The tray body 210 includes one ormore recesses 212 for containing a volume of bioactive glass fibers 10.The volume of bioactive glass fibers may be woven, knitted, intertangledor provided as a loose stack. The volume of bioactive glass fibers mayoptionally include fibers of other compositions, such as antimicrobialsilver, polymers, or alternate glass compositions, and may alsooptionally include particulate matter or particulate of the samebioactive glass composition, or alternate compositions such as alternateglass, metal, metal oxide, medicinal, nutritive, and/or antimicrobial orthe like. The kit may also optionally include a liquid, such as salineor collagen gel, for mixing with the bioactive glass volume.

In operation, the surgeon removes the lid 220 of the kit 200 and removesa portion of the included bioactive glass material 10. The bioactiveglass material may then be shaped and sized by the surgeon for insertioninto a bony cavity. This process may involve the addition of anappropriate liquid to the bioactive glass material, such as saline,collagen gel, plasma, blood, or the like, to achieve a desired degree ofpliability and/or structural integrity. Once the bioactive glassmaterial is sized and shaped as desired, it is inserted into the bonycavity. This process may be done as a single operation or as a series ofsteps.

FIGS. 6A to 6D illustrate additional embodiments of a mold tray that mayform a part of the surgical kit. As in the previous embodiment, the moldtrays may comprise a base component and a lid component configured tofit onto the base component to form an enclosed container. Each of thetrays may be provided with a fluid port. More than one fluid port may beprovided on a tray. The fluid ports allow filling of the material aswell as access to introduce a fluid or wetting agent as previouslydescribed to the material. Further, while the present embodiments showmold trays that have a single lid portion, it is understood thatmultiple lids may be provided for use with a single tray portion.Alternatively, a tray portion may be used without a lid portion. Forexample, the tray portion may include either one side that is open orthe tray portion may be a hollow shell with at least one port to allowfilling of the material and introduction of the fluid or wetting agent.

The mold tray may be sterile. In addition, the base component and lidcomponent form an enclosed container when attached together. The lidcomponent may further include tabs for ease of handling. Each of thebase and lid components have corresponding depressed or raised portionsto form a predefined molded shape or well. The base component may havemore than one preformed well for creating a shaped mold. That shape maybe, for example, a rectangle, square, disc, crescent, star, wave,diamond, C-shape, W-shape, S-shape, or T-shape, as shown in FIGS. 6B-6D.Further, the predefined molded shape may have rounded edges to create asmooth implant. Alternatively, the predefined molded shape may have atapered leading edge for ease of implantation. The molded tray may alsobe disposable.

An exemplary kit 300 is shown in FIG. 6A having a mold tray 310 thatallows a lid similar to 220 to be snap-fitted on the tray 310. The moldtray 310 may include a well 312 as well as a fluid port 330. These fluidports 330 may also serve as finger depressions or finger rests, in orderto further facilitate handling. The tray 310 may further include a tab340 for additional ease of handling. Another exemplary kit 400 is shownin FIG. 6B having a mold tray 410 containing dual wells, 412 a and 412b, along with a fluid port 430. The dual wells allow more than oneimplant 20 to be created with the same mold tray 410.

FIG. 6C illustrates another exemplary embodiment of a surgical kit 500of the present disclosure. The kit 500 may include a mold tray 510having two wells 512 a, 512 b for creating two shaped implants 20. Fluidports 530 may be provided for ease of introducing a wetting agent to thefibrous material. FIG. 6D shows yet another exemplary embodiment of asurgical kit 600 of the present disclosure having a mold tray 610 with ashaped well 612 and including a plurality of fluid ports 630 surroundingthe well 612.

There are clinical advantages to providing a surgical kit of the presentdisclosure. For instance, a closed system comprising the mold tray withits corresponding tray and lid portions allows the user to keep thegraft material cohesive. Further, the system allows for hands-freeoperation in the sense that there is no contact with the graft materialuntil it is ready to be used for surgery. This reduces the chances ofinfection, since the mold tray may also serve as a protective containerfor the graft material and prevent handling prior to use.

Another advantage of the system of the present disclosure is that theuser can control the porosity of the graft material by controlling theweight of the fibrous material added. Since the density of the basematerial is known, as is the volume of the tray cavity, the overallporosity of the graft material inside the ray can be preciselycalculated and controlled. Furthermore, the system allows the user tocustomize the graft material and create, for example, a graft materialwith multiple porosity regions. Such a material can be produced byadding a layer of material of one porosity into a tray, then adding amaterial of a different porosity onto that first layer. Subsequentlayers or materials of different porosities may be added as needed tocreate a composite of desired porosities. Likewise, various materialsmay be added sequentially to create a stacked or layered composite ofmultiple materials. Thus, it is possible to create a materialcomposition having different materials and different porosity gradientsor regions throughout the composition.

There are a number of ways to form the final molded or shaped product.For example, a force may be applied to the lid(s) to compress or squeezethe fibrous material into the well(s) of the tray to create the desiredshape. The force applied may be from manual pressure, or from vacuumpressure. Or, the force may be simply of filling the mold tray with thematerial. In one embodiment, the applied force compresses the porous,fibrous composition. The composition may remain compressed after theforce has been removed.

An exemplary method for loading and shaping the fibrous material 10 isillustrated in FIGS. 7A-7L. FIG. 7A shows a loading container 710 andlid 720 for receiving the ultraporous, fibrous graft material 10 of thepresent disclosure. The lid 720 may be configured for sliding engagementwith the container 710, as shown in FIG. 7B. Of course, it is understoodthat the lid 720 and container 710 may be configured in other ways toallow easy opening and removal, such as for example, snap-fittedengagement, hinged engagement or other frictional engagements as isknown in the art. The fibrous graft material 10 may be loaded inside theclosed container 710 as shown in FIG. 7C, and compressed inside thecontainer 710 such as with a machine press 730 or other type of press.

After the fibrous material 10 is loaded inside the container 710, thematerial can be transferred to the mold tray 310 of a surgical kit, asshown in FIG. 7D. A base frame 740 may be provided having an openingsufficiently sized and shaped for receiving the container 710, while theframe 740 itself can be configured to seat onto the mold tray 310. Asshown in FIGS. 7D and 7E, the base frame 740 may be seated inside one ofthe recesses formed in the mold tray 310, and allow the container 710loaded with the fibrous material 10 to be securely placed over theimplant well of the mold tray. The container 710 is placed onto the baseframe 740 with the open end facing towards the mold tray 310, such thatremoval of the lid 720 exposes the loaded fibrous material 10 as shownin FIG. 7F.

To compress the fibrous material 10 in the container 710 into the wellof the mold tray 310, a hand press 750 may be provided. The hand press750 may be sized and shaped to fit neatly within the container 710, asshown in FIG. 7G. Removal of the hand press 750 reveals a partiallycompressed and shaped fibrous material 10, as illustrated in FIG. 7H. Atthis stage, additional compression may be performed on the material 10inside the mold tray 310. For example, as FIGS. 7I-7K show, furthercompression may be effected by hand pressing using the press 750 withthe container 710 removed to avoid any encumbrances, leaving only thebase frame 70 behind. The press 750 may be the same size and shape asthe previous one, or it may have a different size or shape similar tothe desired final product. As shown in FIG. 7L, the final product may bea fibrous material 10 suitably compressed into one of the wells in themold tray 310 and is now ready for clinical use.

In some cases, it may be desirable to partially compress the graftmaterial and then transfer the partially compressed graft material intothe tray for further and final shaping. In other instances, it maysimply be desirable to compress the graft material with a specializedmold or fixture and then shape the compressed material using the moldtray. For instance, the ultra porous fibrous graft material may bemachine pressed prior to transferring to the mold tray. Alternatively,it is also possible to provide a hand press and tray that fits over themold tray, such that you can utilize the hand press to compress theultra porous fibrous graft material into the mold tray without the useof a lid. Accordingly, the steps provided in FIGS. 7A-7L may be used ina variety of combinations to achieve the desired shape while alsoproviding maximum convenience to the user.

In most cases, the deepest recess chamber of the mold tray or press moldtypically has a simple geometry, such as a rectangular block or wedgeshape, such that the so-loaded bone graft material likewise has a simplegeometry. The bone graft material is typically provided as anintertangled or interwoven mass of bioactive glass fibers. The bioactiveglass fibers may be provided in format that is ready to be surgicallyemplaced in a bony cavity (such as a woven or mesh format), or may beprovided in a format that requires additional preparation prior toemplacement (such as a more loosely intertangled format) that requiresthe addition of a liquid, such as saline, glycerol, gelatin, plasma, orcollagen gel or chips, to assist in rendering the mass of bioactiveglass more pliable and structurally unitary. Such liquids may optionallybe included in the kit packaging, or provided separately.

In operation, the surgeon removes the lid of the kit and removes aportion of the included bioactive glass material. The bioactive glassmaterial may then be shaped and sized by the surgeon for insertion intoa bony cavity. This process may involve the addition of an appropriatewetting agent or liquid to the bioactive glass material, such as saline,collagen gel, plasma, naturally occurring fluid such as blood, or thelike, to achieve a desired degree of pliability and/or structuralintegrity. Another suitable wetting agent or liquid may also include abonding agent or glue, such as a bioresorbable glue like carboxyl methylcellulose (CMC) solution. The wetting agent can also serve as a settingmaterial that enhances the mechanical (and thus clinical handling)properties of the graft material. For example, use of a physiologicsetting agent like blood or bone marrow aspirate, where clotting canoccur over time (for example, in the range of about 10-15 minutes), canlead to better physical properties of the mixer. Once the bioactiveglass material is sized and shaped as desired, it is inserted into thebony cavity. This process may be done as a single operation or as aseries of steps.

The bone graft material 10, 110 is typically provided as an intertangledor interwoven mass of bioactive glass fibers. The bioactive glass fibersmay be provided in format that is ready to be surgically emplaced in abony cavity (such as a woven or mesh format), or may be provided in aformat that requires additional preparation prior to emplacement (suchas a more loosely intertangled format) that requires the addition of aliquid, such as saline, glycerol, gelatin, plasma, or collagen gel orchips, to assist in rendering the mass of bioactive glass more pliableand structurally unitary. Such liquids may optionally be included in thekit packaging 200, or provided separately.

Although the bone graft material of the present disclosure is describedfor use in bone grafting, it is contemplated that the graft material ofthe present disclosure may also be applied to soft tissue or cartilagerepair as well. Accordingly, the application of the fibrous graftmaterial provided herein may include many different medical uses, andespecially where new connective tissue formation is desired.

While the present disclosure has been illustrated and described indetail in the drawings and foregoing description, the same is to beconsidered as illustrative and not restrictive in character. It isunderstood that the embodiments have been shown and described in theforegoing specification in satisfaction of the best mode and enablementrequirements. It is understood that one of ordinary skill in the artcould readily make a nigh-infinite number of insubstantial changes andmodifications to the above-described embodiments and that it would beimpractical to attempt to describe all such embodiment variations in thepresent specification. Accordingly, it is understood that all changesand modifications that come within the spirit of the present disclosureare desired to be protected.

1. A method of preparing a dynamic bioactive bone graft implant,comprising: providing a porous, fibrous composition of bioactive glassfibers, wherein the fibers are characterized by fiber diameters rangingfrom about 5 nanometers to about 100 micrometers, and wherein theporosity of the matrix ranges from about 100 nanometers to about 1millimeter; introducing the porous, fibrous composition into a moldtray; and creating a shaped implant with the mold tray.
 2. The method ofclaim 1, further including the step of wetting the composition with afluid.
 3. The method of claim 2, wherein the fluid is saline.
 4. Themethod of claim 2, wherein the fluid is a naturally occurring bodyfluid.
 5. The method of claim 4, wherein the fluid is blood.
 6. Themethod of claim 1, wherein the mold tray comprises a base component anda lid component configured to fit onto the base component to form anenclosed container.
 7. The method of claim 6, wherein the step ofintroducing includes placing the porous, fibrous composition into thebase component, and the step of creating includes manually attaching thelid component to the base component.
 8. The method of claim 6, whereinthe step of introducing includes placing the porous, fibrous compositioninto the base component, and the step of creating includes applying avacuum force after attaching the lid component to the base component. 9.The method of claim 1, further including applying force to compress theporous, fibrous composition.
 10. The method of claim 9, wherein thecomposition remains compressed after the force has been removed.
 11. Akit for preparing a dynamic bioactive bone graft implant, comprising: aporous, fibrous composition of bioactive glass fibers, wherein thefibers are characterized by fiber diameters ranging from about 5nanometers to about 100 micrometers, and wherein the porosity of thematrix ranges from about 100 nanometers to about 1 millimeter; and amold tray including a base component and a lid component configured tonest within the base component, each of the base and lid componentshaving corresponding depressed or raised portions to form a predefinedmolded shape.
 12. The kit of claim 11, wherein the mold tray is sterile.13. The kit of claim 11, wherein the base component and the lidcomponent form an enclosed container when attached together.
 14. The kitof claim 11, wherein the lid component further includes tabs for ease ofhandling.
 15. The kit of claim 11, wherein the mold tray is formed of aclear material for ease of visualization.
 16. The kit of claim 11,wherein the base component has more than one preformed well for creatinga shaped mold.
 17. The kit of claim 11, wherein the mold tray isdisposable.
 18. The kit of claim 11, wherein the porous, fibrouscomposition has an initial surface area greater than a well inside thebase component of the mold tray.
 19. The kit of claim 11, wherein thepredefined molded shape is a rectangle, square, disc, crescent, star,wave, diamond, C-shape, W-shape, S-shape, or T-shape.
 20. The kit ofclaim 11, wherein the predefined molded shape has rounded edges.
 21. Thekit of claim 11, wherein the predefined molded shape has a taperedleading edge for ease of implantation.